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Osteogenic Growth Peptide Fusion Proteins

a technology of growth peptides and fusion proteins, which is applied in the direction of peptide/protein ingredients, peptide/protein fragmentation, depsipeptides, etc., can solve the problems of short half-life of circulation, limited therapeutic potential of novel proteins as well as “old” and well-established proteins, and achieve the effect of improving the physico-chemical properties of proteins and increasing the circulation time of ogp proteins

Inactive Publication Date: 2008-03-13
NOVO NORDISK AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is related to a method of increasing the circulation time of OGP proteins in the body, improving their physico-chemical properties, and using OGP fusion proteins in therapy and pharmaceutical compositions. The invention also includes the use of nucleic acid constructs, vectors, host cells, and transgenic organisms to express OGP fusion proteins. The technical effects of the invention include improved function and stability of OGP proteins, as well as improved delivery and therapeutic efficacy.

Problems solved by technology

However, the therapeutic potential of these novel proteins as well as “old” and well-established proteins is often limited by very short half-life in circulation.

Method used

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  • Osteogenic Growth Peptide Fusion Proteins
  • Osteogenic Growth Peptide Fusion Proteins
  • Osteogenic Growth Peptide Fusion Proteins

Examples

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examples

Cloning

[0175] The following constructs have been made: OGP-hGH (pNNC37) OGP(1-9)-hGH (pNNC37.1), OGP-OGP-hGH (pNNC38), OGP(1-9)-OGP(1-9)-hGH (pNNC38.1), OGP-OGP-OGP-hGH (pNNC38.2), OGP-OGP-NDEMPADLPS-hGH (pNNC39) and OGP(1-9)-OGP(1-9)—NDEMPADLPS-hGH (pNNC39.1).

[0176] Since OGP and variants thereof according to the present invention are fairly short peptides the cloning of OGP-hGH, OGP(1-9)-hGH, OGP-OGP-hGH and OGP(1-9)-OGP(1-9)-hGH utilized OGP encoding DNA oligo linkers for direct cloning into the Nde1 and Sal1 site in the pNNC19 bacterial expression vector that already contains the human growth hormone gene (pNNC19 is based on the commercial available pET11a vector). The OGP encoding sequences was codon optimized for E. coli expression using the Vector Suit NTI programme. When dimeric or trimeric OGP sequences are used, alternate codon usage may be utilized in the repeat to avoid genetic instability and cross hybridization. The oligos containing the dimeric forms of OGP have bee...

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Abstract

Fusion protein comprising a protein to be fused, e.g. a therapeutic protein fused to the C-terminal of osteogenic growth peptide (OGP). The fusion proteins have a prolonged circulation time.

Description

FIELD OF THE INVENTION [0001] The invention relates to osteogenic growth peptide (OGP) fusion proteins. The invention also relates to methods of increasing the circulation time of therapeutic proteins by fusing them to OGP or variants thereof, and to therapeutic method comprising the administration of OGP fusion proteins. BACKGROUND OF THE INVENTION [0002] Osteogenic growth peptide (OGP) is a tetradecapeptide identical to the C-terminal amino acid sequence 89-102 of Histone H4. The amino acid sequence of OGP is Ala-Leu-Lys-Arg-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-Gly-Gly (SEQ ID NO:33). OGP is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. The plasma levels of OGP depend e.g. on age but it is present in a high abundance, up to 480-4460 μM. However, 80-90% of the OGP is non-covalently bound to other plasma proteins, the most important of which is α2-macroglobulin (α2M) [Biochem., 36, 14883-14888, 1997]. [0003] Bound OGP is inactive, but upon...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00A61P43/00C07H21/04C07K16/00C12N15/00C12N5/00C12P21/04C12N15/62
CPCC12N15/62C07K2319/31A61P1/16A61P3/04A61P5/06A61P9/00A61P11/00A61P13/12A61P15/08A61P17/02A61P19/00A61P19/02A61P19/10A61P25/24A61P25/28A61P29/00A61P31/18A61P39/02A61P43/00
Inventor BLUME, NIELSSU, JINGMADSEN, KJELDJOHANSEN, NILS LANGELANDIVERSEN, LARS FOGH
Owner NOVO NORDISK AS